2. Academic Validation
  3. JMJD5 cleaves monomethylated histone H3 N-tail under DNA damaging stress

JMJD5 cleaves monomethylated histone H3 N-tail under DNA damaging stress

  • EMBO Rep. 2017 Dec;18(12):2131-2143. doi: 10.15252/embr.201743892.
Jing Shen 1,  Xueping Xiang 1,  Lihan Chen 2,  Haiyi Wang 2,  Li Wu 2,  Yanyun Sun 2,  Li Ma 3,  Xiuting Gu 2,  Hong Liu 1,  Lishun Wang 2,  Ying-Nian Yu 1,  Jimin Shao 4,  Chao Huang 5 6,  Y Eugene Chin 5 3 6
Affiliations

Affiliations

  • 1 Department of Pathology, Zhejiang University School of Medicine, Hangzhou Zhejiang, China.
  • 2 Institute of Health Sciences, Chinese Academy of Sciences-Jiaotong University School of Medicine, Shanghai, China.
  • 3 Department of Surgery, Brown University School of Medicine-Rhode Island Hospital, Providence, RI, USA.
  • 4 Department of Pathology, Zhejiang University School of Medicine, Hangzhou Zhejiang, China shaojimin@zju.edu.cn c_huang_bio@msn.com yechin@sibs.ac.cn.
  • 5 Institute of Health Sciences, Chinese Academy of Sciences-Jiaotong University School of Medicine, Shanghai, China shaojimin@zju.edu.cn c_huang_bio@msn.com yechin@sibs.ac.cn.
  • 6 Translation Medicine Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
PMID: 28982940 DOI: 10.15252/embr.201743892
Abstract

The histone H3 N-terminal protein domain (N-tail) is regulated by multiple posttranslational modifications, including methylation, acetylation, phosphorylation, and by proteolytic cleavage. However, the mechanism underlying H3 N-tail proteolytic cleavage is largely elusive. Here, we report that JMJD5, a Jumonji C (JmjC) domain-containing protein, is a Cathepsin L-type protease that mediates histone H3 N-tail proteolytic cleavage under stress conditions that cause a DNA damage response. JMJD5 clips the H3 N-tail at the carboxyl side of monomethyl-lysine (Kme1) residues. In vitro H3 peptide digestion reveals that JMJD5 exclusively cleaves Kme1 H3 Peptides, while little or no cleavage effect of JMJD5 on dimethyl-lysine (Kme2), trimethyl-lysine (Kme3), or unmethyl-lysine (Kme0) H3 Peptides is observed. Although H3 Kme1 Peptides of K4, K9, K27, and K36 can all be cleaved by JMJD5 in vitro, K9 of H3 is the major cleavage site in vivo, and H3.3 is the major H3 target of JMJD5 cleavage. Cleavage is enhanced at gene promoters bound and repressed by JMJD5 suggesting a role for H3 N-tail cleavage in gene expression regulation.

Keywords

H3K9me1; Histone H3; JMJD5; N‐tail cleavage.

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